We evaluated the efficacy of a full-scale combined biophysicochemical system for treatingmolasses-based bioethanol wastewater in terms of organic substances, nutrient, and dark brown color removal. The main organic removal unit, i.e., the upflow anaerobic sludge blanket (UASB) reactor, achieved 80.7% removal and 4.3 Nm3 methane production per cubic meter of wastewater with a hydraulic retention time of 16.7 h. Downflow hanging sponge (DHS) reactors were important in reducing the biochemical oxygen demand (BOD), and the lowest possible organic waste intake prevented excessive biomass formation. The BOD removal efficiency was 71.2–97.9%. The denitrification upflow anaerobic fixed bed (UFB) reactor achieved 99.2% total nitrogen removal. Post-physicochemical membrane treatment reduced the total phosphate, color, and remaining organic matter by 90.4%, 99.1%, and 99.8%, respectively. We analyzed the microbial diversity of the sludge from the UASB reactors. Methanosaeta was the dominant archaeal genus in the system, followed by Methanolinea, Methanomicrospillum, Caldiserica, Bacteroidetes, and Deltaproteobacteria.